UNIPROT:P20366 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

Query: UNIPROT:P20366 (substance P)
21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neutral endopeptidase (NEP, EC 3.4.24.11), angiotensin-converting enzyme (ACE, EC 3.4.15.1) and carboxypeptidase N (CPN, EC 3.4.17.3) are potentially important enzymes which regulate the degradation of neuropeptides, such as bradykinin (BK) and substance P (SP), in the respiratory mucosa. Some neuropeptides are also degraded by these enzymes in vitro and in vivo. We investigated the localization of these enzymes in the human nasal mucosa by an indirect immunohistochemical technique (immunogold silver staining). NEP-immunoreactive areas were present in the epithelium, the serous cells of the submucosal glands, and the endothelial cells of small vessels. The epithelium and the serous cells were the predominant areas of NEP immunoreactivity in the nasal mucosa. ACE-immunoreactive areas were seen in the outer layer of the epithelium, the endothelial cells of vessels, and widely distributed in the superficial lamina propria. The endothelial cells of the vessels showed maximum positive intensity to ACE. CPN-immunoreactive areas were observed in the epithelium, the endothelium of vessels and the superficial lamina propria, except for the gland cells. The superficial lamina propria exhibited maximum immunoreactivity for CPN. We observed that the enzymes were widely distributed in the nasal mucosa. The epithelium, including the epithelial cells and glycocalyx, contains all three enzymes. These enzymes play an important role in the mucosal immunity of the respiratory mucosa by degrading active neuropeptides. These results show that NEP secretion is regulated by a glandular, cholinergic control. On the other hand, ACE and CPN secretion are regulated by vascular permeability.
...
PMID:Immunological localization of neuropeptide-degrading enzymes in the nasal mucosa. 783 83

Medium spiny projection neurons of the striatum consist of two major neuropeptide-specific types, one type containing substance P and another type containing enkephalin. Both of these types have been shown to receive dopaminergic input onto their perikarya and proximal dendrites. However, whether each of these types receives direct dopaminergic input onto distal dendritic shafts and onto dendritic spines has not been explored in depth. In the present study, we used electron microscopic immunohistochemical double-label techniques to examine the synaptic organization of dopaminergic input onto enkephalin-positive (ENK+) striatal neurons in pigeons, in whom ENK+ striatal perikarya, dendritic shafts and spines can be readily labeled. Antibodies against tyrosine hydroxylase were used to label dopaminergic terminals using a silver-intensified immunogold method. ENK+ neurons were labeled using diaminobenzidine. We found that dopaminergic terminals make appositions and form symmetric synapses with the perikarya, dendritic shafts, and dendritic spine necks of ENK+ striatal neurons. Thus, nigral dopaminergic neurons provide a monosynaptic input onto ENK+ striatal neurons in a manner similar to that described previously by us for substance P-positive striatal medium spiny neurons.
...
PMID:Dopaminergic terminals form synaptic contacts with enkephalinergic striatal neurons in pigeons: an electron microscopic study. 805 33

Novel monoclonal antibodies to human chromogranin A (CgA) and chromogranin B (CgB) were used to investigate the presence of immunoreactive (-IR) elements in the alimentary tract of the green frog Rana esculenta. Numerous CgA-IR and a few CgB-IR endocrine cells were found within the gut mucosa, from the oesophagus to the cloaca, with some local differences in density. Co-localization studies demonstrated that they were co-stored in almost all the serotonin-IR, the amylin-IR or islet amyloid polypeptide-IR cells and in the peptide tyrosine tyrosine-IR cells located proximal to the pylorus, but not in those located in more caudal tracts. No other co-localization was demonstrated; substances investigated included somatostatin, substance P, gastrin/cholecystokinin, glucagon, glycentin, bombesin, secretin and neurotensin. CgA-IR and CgB-IR cells nearly always displayed argyrophilia with the Grimelius silver method.
...
PMID:Immunohistochemical localization of chromogranin A and B in the endocrine cells of the alimentary tract of the green frog, Rana esculenta. 808 25

The localization and distribution of vasoactive intestinal polypeptide (VIP), peptide histidine methionine (PHM), the novel peptide helospectin, neuropeptide tyrosine (NPY) and its C-flanking peptide (C-PON), substance P and calcitonin gene-related peptide (CGRP) were studied in the middle and inferior turbinate of the human nose using sensitive immunocytochemical and radioimmunological methods. For light microscopy, double immunofluorescence and immunogold-silver staining methods were applied. Ultrastructural immunoelectronmicroscopy was performed using a pre-embedding method. In addition, semithin Epon resin sections were immunostained. The concentrations of VIP, NPY, CGRP, substance P and neurokinin A were measured using radioimmunological methods. A dense network of autonomic and peptidergic nerve fibers in the normal human nasal mucosa was demonstrated. Colocalization studies showed the coexistence of peptides with components of the autonomic nervous system. Scattered chromogranin A-, CGRP and bombesin-flanking peptide (BFP)-immunoreactive endocrine-like cells were detected within the lamina propria and in groups within exocrine ducts. Highest radioimmunoassay (RIA) tissue concentrations were detected for VIP, followed by NPY, substance P, CGRP and neurokinin A.
...
PMID:Autonomic and peptidergic innervation of human nasal mucosa. 810 Jan 9

In situ hybridization histochemistry was used to analyse the expression of the messenger RNAs encoding for enkephalin, substance P and dynorphin in the striatum of normal rats, rats subjected to a unilateral 6-hydroxydopamine lesion of the mesostriatal dopamine pathway and lesioned rats bearing intrastriatal transplants of fetal nigral neurons. About half of the rats in each group received twice-daily subcutaneous injections of 5 mg/kg apomorphine and the other half received control injections of saline, for nine days. Three hours after the last injection, the rats were killed by decapitation. Cryostat sections through the striatum were incubated with, 35S-labeled oligodeoxyribonucleotide probes hybridizing with preproenkephalin, preprotachykinin or prodynorphin messenger RNA. One additional series of sections was incubated with [3H]GBR 12935 in order to label dopamine uptake sites. Quantitative evaluation of the hybridization signal was performed both at the macroscopic level (autoradiographic film analysis) and at the cellular level (optical density of silver grains over identified cells). The grafted nigral neurons reversed the lesion-induced up-regulation of preproenkephalin messenger RNA in the whole striatal complex. By contrast, the graft-induced effect on the lesion-induced down-regulation of preprotachykinin messenger RNA was restricted to the region of the host striatum where the graft-derived dopamine fibers exhibited their densest distribution (up to 0.5 mm from the border of the grafts). However, following chronic treatment with apomorphine, preprotachykinin messenger RNA expression approached control levels in a wider portion of the grafted striata (up to 1 mm from the border of the grafts). Basal prodynorphin messenger RNA expression, which was also down-regulated in the lesioned striata, was only partially restored by the transplants. Repeated injections of apomorphine enhanced prodynorphin messenger RNA in the lesioned striata to levels several fold higher than normal. This massive increase in prodynorphin messenger RNA expression was completely prevented by the transplants over a large volume of the host striatum (> 1 mm from the graft-host border), but a trend towards an abnormally high prodynorphin messenger RNA expression was still present in peripheral striatal areas that were not reached by graft-derived dopamine fibers. The present results indicate that fetal nigral neurons transplanted to the 6-hydroxydopamine-lesioned striatum have differential effects on the activity of enkephalin-containing (i.e. mainly striatopallidal) and substance P- or dynorphin-containing (i.e. mainly striatonigral) neurons. An inhibitory control over the activity of striatopallidal neurons is completely restored by the grafts, even in non-reinnervated striatal regions, suggesting that neurohumoral mechanisms underlie this effect.(ABSTRACT TRUNCATED AT 400 WORDS)
...
PMID:Neuropeptide messenger RNA expression in the 6-hydroxydopamine-lesioned rat striatum reinnervated by fetal dopaminergic transplants: differential effects of the grafts on preproenkephalin, preprotachykinin and prodynorphin messenger RNA levels. 811 38

As part of an ongoing investigation devoted to understanding the pathogenesis of senile plaques, we employed histochemical and immunocytochemical techniques to examine the distribution and cytologic features of acetylcholinesterase (AChE), choline acetyltransferase (ChAT), somatostatin (SOM), neurotensin (NT) and substance P (SP) containing fibers and neurons within the amygdala of: (1) patients with Alzheimer's disease (AD); (2) age-matched non-demented controls (NC); and (3) a group of non-demented cases, who upon postmortem neuropathologic examination exhibited sufficient numbers of senile plaques to be classified as AD. This latter group was referred to as high plaque non-demented (HPND). For every case, the distribution of immunolabeled fibers and neurons were determined for each transmitter throughout the various subnuclei of the amygdala. In addition, in the AD and HPND cases the topographic distribution of senile plaques was determined throughout the amygdala using thioflavine-S and Bielschowsky silver methods. In the amygdala, the distribution and density of senile plaques were not bound by conventional cytoarchitectural groupings but rather were most dense in the ventromedial regions of the amygdala with decreasing density in dorsal and lateral directions. Importantly, the density and distribution of senile plaques failed to correlate with the normal topography and/or density of the various peptidergic or cholinergic fibers within the amygdala. The finding that plaques do not correlate with the topographic distribution of any specific transmitter system suggests that plaques likely do not arise from the degeneration of a single neurotransmitter system (i.e., the cholinergic system). However, the finding that in AD a transmitter is most markedly depleted in regions of greatest plaque density, suggests certain constituents of the plaque (e.g. beta-amyloid) may be contributing to the degeneration of local fibers. The extent to which a transmitter was depleted in AD patients varied considerably among those four investigated with the cholinergic and NT systems displaying the most dramatic reductions, followed by SP and SOM. Despite these differential reductions in fiber density, all four neurotransmitters were found localized within dystrophic neurites and in most instances these dystrophic neurites were associated with thioflavine-positive senile plaques. In contrast to the AD cases, the HPND cases were characterized by no significant reductions in immunolabeled fibers, although immunostained dystrophic neurites were very prevalent in the HPND cases. These data suggest that dystrophic neurites occur very early in the disease process and likely precede the actual loss of fibers when or if it occurs.(ABSTRACT TRUNCATED AT 400 WORDS)
...
PMID:Immunocytochemical distribution of peptidergic and cholinergic fibers in the human amygdala: their depletion in Alzheimer's disease and morphologic alteration in non-demented elderly with numerous senile plaques. 824 91

The innervation of the navicular bone (os sesamoideum distale) and its suspensory ligaments (ligamenta sesamoidea collateralia) (CSL) or proximal suspensory ligament and the ligamentum sesamoideum distale impar or the distal sesamoidean impar ligament (DS-impar ligament) was examined using combined anatomical techniques of silver impregnation and immunocytochemistry. Silver impregnation studies revealed an abundance of nerve fibres present in both the CSL and DS-impar ligament with the latter having relatively more nerve fibres. These silver-impregnated nerves coursed parallel to and were associated with the vasculature rather than appearing to innervate the vessels. Immunocytochemistry identified several sensory-related neuropeptides (calcitonin gene-related peptide (CGRP), substance P (SP) and neurokinin A (NKA)) in the nerves of the navicular bone and suspensory ligaments. More peptidergic nerves were evident within the synovial membrane and loose connective tissue in the dorsal part than in the palmar aspect of the CSL. In the CSL along the synovial membrane bordering the distal interphalangeal joint, the CGRP, SP and NKA were present in the nerves of vessels as well as the intimal layer of the distal interphalangeal joint. In the DS-impar ligament, there were many more nerves innervating vessels and the synovial membrane between the navicular bone and the third phalanx than were present in these structures in the CSL. Nerves with all 3 peptides entered the navicular bone via the proximal border and the distal groove to innervate the perichondrium, trabeculae and osteons. SP-like nerves also innervated the cortical bone underlying the articular cartilage. We suggest that these sensory nerve peptides contribute to the pathology of the navicular syndrome. The distribution of the nerves in the CSL and the DS-impar ligament could explain the clinical effects of local anaesthetics injected into the distal interphalangeal joint.
...
PMID:A silver-impregnation and immunocytochemical study of innervation of the distal sesamoid bone and its suspensory ligaments in the horse. 854 41

We have used a pharmacologic mediator to open intercellular connections in selected vessels to allow liposomes to escape from the blood stream and to extravasate into tissues that have appropriate receptors. We have examined the effects of substance P (SP), a peptide known to increase vascular permeability in selected tissues, such as trachea, esophagus, and urinary bladder in rats. We used quantitative fluorescence analysis of tissues to measure two fluorescent markers, one attached to the lipid (rhodamine-phosphatidylethanolamine) and another, doxorubicin (an anti-tumor drug), encapsulated within the aqueous interior. We have also examined the deposition of liposomes microscopically by the use of encapsulated colloidal gold and silver enhancement. Analysis of the biochemical and morphological observations indicate the following: (i) Injection of SP produces a striking increase in both liposome labels, but only in tissues that possess receptors for SP in postcapillary venules; (ii) liposome material in these tissues has extravasated and is found extracellularly near a variety of cells beyond the endothelial layer over the first few hours; (iii) 24 h following injection of liposomes and SP, liposome material is found in these tissues, localized intracellularly in both endothelial cells and macrophages. We propose that appropriate application of tissue-specific mediators can result in liposome extravasation deep within tissues that normally do not take up significant amounts of liposomes from the blood. Such liposomes are able to carry a variety of pharmacological agents that can be released locally within selected target tissues for therapeutic purposes.
...
PMID:Increased liposome extravasation in selected tissues: effect of substance P. 869 75

The cellular expression of the mRNAs encoding the dopamine D1 receptor, dopamine D2 receptor and the neuropeptides enkephalin and substance P was determined in fresh frozen sections of human post-mortem caudate nucleus from control and schizophrenic brains using the technique of radioactive in situ hybridisation coupled with computer-assisted image analysis. Measurements of silver grain densities and mean cross-sectional somatic areas revealed no significant differences in the expression of any of these four gene transcripts. Further, cell count estimates revealed that each of these four mRNAs was expressed by approximately 20% of caudate cells (neurones and glia) in both control and schizophrenic tissue. These data demonstrate that the cellular expression of the dopamine D1 and D2 receptors and the neuropeptides enkephalin and substance P mRNAs are stable post mortem and that the relative cellular abundance of these mRNAs is not altered in the caudate nucleus of schizophrenic brains when compared to controls. These findings draw into focus the possible sites of action of clinically prescribed neuroleptics and suggest that chronic neuroleptic treatment of patients displaying negative schizophrenic symptoms may 're-set' an underlying neurochemical imbalance within the caudate nucleus.
...
PMID:Dopamine D1 receptor, D2 receptor, proenkephalin A and substance P gene expression in the caudate nucleus of control and schizophrenic tissue: a quantitative cellular in situ hybridisation study. 875 Aug 94

Major complications arising from diabetes mellitus include neuropathic pain and altered peripheral inflammatory responses. Somatostatin (SOM), calcitenin gene-related peptide (CGRP), and substance P (SP) are neuropeptides that modulate pain responses transmitted by primary sensory afferents, the cell bodies of which are located in the dorsal root ganglion (DRG). Thus, the goal of the present study was to determine whether the diabetic condition is associated with altered neuropeptide gene expression in lumbar DRG of the rat. We employed an established animal model in which streptozotocin (STZ, 55 mg/kg) is administered to 6 week-old rats. The hallmark symptoms of hyperglycemia (blood glucose > 400 mg/dl), polydipsia, polyuria, and severe weight loss were maximal at 6 weeks postadministration, at which time animals were sacrificed. For determination of peptide encoding mRNAs distributed in DRG neurons, in situ hybridization histochemistry utilizing S-end-labeled oligonucleotides complimentary to sequences of preprosomatostatin (PPSOM), preprocalcitonin gene related peptide (PPCGRP), preprotachykinin (PPT), or preproneuropeptide Y (PPNPY) mRNA was performed. Silver grains were detected overlying DRG cells by autoradiography on sections of tissue counterstained with thionin. Semiquantitative analysis of differences in silver grain signal were made using an image analysis system, which expressed signals as fCi/microns2. In diabetic rats there was a significant decrease in DRG PPSOM (54%, p < 0.01), and PPCGRP (33%. p < 0.05) mRNA hybridization from the normal values PPT mRNA hybridization signal and SP-like immunoreactivity were not significantly changed in diabetic rat DRGs compared to control. In contrast, there was an increase in the number of cells labeled with PPNPY hybridization in DRG from diabetic rats. These data suggest that CGRP and SOM synthesis in primary sensory neurons is reduced in STZ-induced diabetic rats. These changes could contribute to the painful neuropathies and altered inflammatory responses seen in diabetes mellitus.
...
PMID:Streptozotocin-induced diabetes is associated with altered expression of peptide-encoding mRNAs in rat sensory neurons. 889 22

<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>